This project will continue our investigations of human intestinal function and focus on the mechanisms of diarrhea. Phase I is a multidisciplinary study of short chain fatty acids (SCFA) arising from intestinal bacterial fermentation of carbohydrates. SCFA are the major constituent of stool water in health and many diarrheal states. Methods have been developed for measuring total SCFA (cation followed by anion exchange resin, followed by electrometric titration) and for identification and quantitation of individual SCFA's by gas-liquid chromatography. Intestinal SCFA transport and its effect on membrane potential, Na ion, and sugar transport is being studied in rat and man. In man, absorption rates and possible effects of SCFA on flow velocity and secretion rates will be investigated in the small and large intestine. Rates of SCFA formation will be determined during intestinal sugar perfusions. Finally, the composition of stool water ultrafiltrates will be determined in health and disease in an attempt to classify diarrheal diseases by the "stool ionogram." Phase II represents thorough pathophysiologic investigations of patients with diarrhea caused by abnormalities of the pancreatic islets with overproduction of various enteric hormones.